The effects of GSK-3β blockade on ketamine self-administration and relapse to drug-seeking behavior in rats

2015 ◽  
Vol 147 ◽  
pp. 257-265 ◽  
Author(s):  
Xianni Huang ◽  
Kunyu Huang ◽  
Wenhui Zheng ◽  
Thomas J.R. Beveridge ◽  
Shujun Yang ◽  
...  
Keyword(s):  
Self Administration ◽  
Drug Seeking ◽  
Seeking Behavior ◽  
Gsk 3Β

Accumbal Neural Responses During the Initiation and Maintenance of Intravenous Cocaine Self-Administration

2004 ◽  
Vol 91 (1) ◽  
pp. 314-323 ◽  
Author(s):  
Laura L. Peoples ◽  
Kevin G. Lynch ◽  
Jamie Lesnock ◽  
Nidhi Gangadhar
Keyword(s):  
Drug Effects ◽  
Extracellular Recording ◽  
Neural Responses ◽  
Self Administration ◽  
Drug Seeking ◽  
Recording Session ◽  
Seeking Behavior ◽  
Excitatory Responses ◽  
Drug Free ◽  
Intravenous Cocaine

During a chronic extracellular recording session, animals with a history of cocaine self-administration were allowed to initiate drug seeking under drug-free conditions. Later, in the same recording session, animals engaged in intravenous cocaine self-administration. During the drug-free period, 31% of 70 accumbal neurons showed a significant increase in average firing rate in association with either or both the exposure to cues that signaled the onset of cocaine availability and the subsequent onset of drug-seeking behavior. The neurons that showed an average excitatory response during the drug-free period were the only group of neurons that showed an average excitatory phasic response to cocaine-reinforced lever presses during the drug self-administration session. A majority of the neurons that were activated during the drug-free period, like the majority of other neurons, showed decreases in average firing in response to self-administered cocaine. However, the neurons that were activated during the drug-free period maintained a higher rate of firing throughout the self-administration session than did other accumbal neurons. The data of the present study are consistent with the conclusion that accumbal neurons contribute to, or otherwise process, initiation of drug seeking under drug-free conditions and that they do so via primarily excitatory responses. Furthermore, there is continuity between the drug-free and -exposed conditions in neural responses associated with drug seeking. Finally, the data have potential implications for understanding mechanisms that transduce accumbal-mediated drug effects that contribute to drug addiction.

scholarly journals Drug-associated cues and drug dosage contribute to increased opioid seeking after abstinence

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mary Tresa Zanda ◽  
Gabriele Floris ◽  
Stephanie E. Sillivan
Keyword(s):  
Drug Dosage ◽  
Opioid Use Disorder ◽  
Drug Intake ◽  
Opioid Use ◽  
Self Administration ◽  
Drug Seeking ◽  
Drug Cues ◽  
Rehabilitation Programs ◽  
Key Factor ◽  
Seeking Behavior

AbstractPatients with opioid use disorder experience high rates of relapse during recovery, despite successful completion of rehabilitation programs. A key factor contributing to this problem is the long-lasting nature of drug-seeking behavior associated with opioid use. We modeled this behavior in a rat drug self-administration paradigm in which drug-seeking is higher after extended abstinence than during the acute abstinence phase. The goal of this study was to determine the contribution of discrete or discriminative drug cues and drug dosage to time-dependent increases in drug-seeking. We examined heroin-seeking after 2 or 21 days of abstinence from two different self-administration cue-context environments using high or low doses of heroin and matched animals for their drug intake history. When lower dosages of heroin are used in discriminative or discrete cue protocols, drug intake history contributed to drug-seeking after abstinence, regardless of abstinence length. Incubation of opioid craving at higher dosages paired with discrete drug cues was not dependent on drug intake. Thus, interactions between drug cues and drug dosage uniquely determined conditions permissible for incubation of heroin craving. Understanding factors that contribute to long-lasting opioid-seeking can provide essential insight into environmental stimuli and drug-taking patterns that promote relapse after periods of successful abstinence.

scholarly journals Dynamic CRMP2 regulation of CaV2.2 in the prefrontal cortex contributes to the reinstatement of cocaine seeking

2019 ◽  
Author(s):  
William C. Buchta ◽  
Aubin Moutal ◽  
Bethany Hines ◽  
Constanza Garcia-Keller ◽  
Alexander C.W. Smith ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Treatment Options ◽  
Health Concern ◽  
Self Administration ◽  
Drug Seeking ◽  
Binding Partner ◽  
Cocaine Seeking ◽  
Seeking Behavior ◽  
Medial Pfc

AbstractCocaine addiction is a major health concern with limited effective treatment options. A better understanding of mechanisms underlying relapse may help inform the development of new pharmacotherapies. Emerging evidence suggests that collapsin response mediator protein 2 (CRMP2) regulates presynaptic excitatory neurotransmission and contributes to pathological changes during diseases, such as neuropathic pain and substance use disorders. We examined the role of CRMP2 and its interactions with a known binding partner, CaV2.2, in cocaine-seeking behavior. We employed the rodent self-administration model of relapse to drug-seeking and focused on the prefrontal cortex (PFC) for its well-established role in reinstatement behaviors. Our results indicated that repeated cocaine self-administration resulted in a dynamic and persistent alteration in the PFC expression of CRMP2 and its binding partner, the CaV2.2 (N-type) voltage-gated calcium channel. Following cocaine self-administration and extinction training, the expression of both CRMP2 and CaV2.2 was reduced relative to Yoked saline controls. By contrast, cued-reinstatement potentiated CRMP2 expression and increased CaV2.2 expression above extinction levels. Lastly, we utilized the recently developed peptide myr-TAT-CBD3 to disrupt the interaction between CRMP2 and CaV2.2 in vivo. We assessed the reinstatement behavior after infusing this peptide directly into the medial PFC and found that it decreased cue-induced reinstatement of cocaine seeking. Taken together, these data suggest that neuroadaptations in the CRMP2/CaV2.2 signaling cascade in the PFC can facilitate drug seeking behavior. Targeting such interactions has implications for the treatment of cocaine relapse behavior.

scholarly journals The Molecular-Container Calabadion-2 Prevents Methamphetamine-Induced Reinstatement in Rats: A Potential Approach to Relapse Prevention?

2020 ◽  
Vol 23 (6) ◽  
pp. 401-405 ◽  
Author(s):  
Michael Z Leonard ◽  
Paul Rostin ◽  
Kevin P Hill ◽  
Stephanie D Grabitz ◽  
Matthias Eikermann ◽  
...  
Keyword(s):  
Relapse Prevention ◽  
Preclinical Model ◽  
Priming Dose ◽  
Self Administration ◽  
Drug Seeking ◽  
Molecular Container ◽  
Seeking Behavior ◽  
Multi Phase ◽  
Pharmacokinetic Approach

Abstract Background Reexposure to methamphetamine with a single “priming dose” can trigger intense cravings and precipitate relapse in methamphetamine-dependent individuals. The acyclic cucurbit[n]uril “molecular container” calabadion-2 shows a high affinity to bind and sequester methamphetamine in vitro and attenuates its locomotor-stimulating effect in rats. The present study investigates whether pretreatment with calabadion-2 is sufficient to prevent the reinstatement of drug seeking by a priming dose of methamphetamine in rats. Methods Male Long-Evans rats were trained to self-administer i.v. methamphetamine (0.06 mg/kg/infusion). Following 10 days of stable self-administration, rats underwent extinction training and were subsequently tested on a multi-phase reinstatement procedure. Drug-primed reinstatement sessions (0.3 mg/kg methamphetamine, i.v.) were preceded by either saline or calabadion-2 (130 mg/kg). Additional reinstatement tests were conducted after administration of yohimbine (1.0 mg/kg, i.v.) to define the pharmacological specificity of calabadion-2. Results Pretreatment with calabadion-2 significantly attenuated methamphetamine-induced reinstatement of responding. Cal2 did not affect drug-seeking behavior stimulated by the pharmacological stressor yohimbine, indicating a mechanism of action specific to methamphetamine. Conclusions These results demonstrate the effectiveness of calabadion-2 in a preclinical model relapse-like behavior. With further structural optimization, molecular containers may provide a novel and efficacious pharmacokinetic approach to relapse prevention for methamphetamine-dependent individuals.

scholarly journals S-Equol mitigates motivational deficits and dysregulation associated with HIV-1

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kristen A. McLaurin ◽  
Sarah J. Bertrand ◽  
Jessica M. Illenberger ◽  
Steven B. Harrod ◽  
Charles F. Mactutus ◽  
...  
Keyword(s):  
Therapeutic Effects ◽  
Self Administration ◽  
Drug Seeking ◽  
Motivated Behavior ◽  
Seeking Behavior ◽  
Underlying Basis ◽  
History Of ◽  
Potential Clinical Utility ◽  
And Control ◽  
Hiv 1

AbstractMotivational deficits (e.g., apathy) and dysregulation (e.g., addiction) in HIV-1 seropositive individuals, despite treatment with combination antiretroviral therapy, necessitates the development of innovative adjunctive therapeutics. S-Equol (SE), a selective estrogen receptor β agonist, has been implicated as a neuroprotective and/or neurorestorative therapeutic for HIV-1 associated neurocognitive disorders (HAND); its therapeutic utility for motivational alterations, however, has yet to be systematically evaluated. Thus, HIV-1 transgenic (Tg) and control animals were treated with either a daily oral dose of SE (0.2 mg) or vehicle and assessed in a series of tasks to evaluate goal-directed and drug-seeking behavior. First, at the genotypic level, motivational deficits in HIV-1 Tg rats treated with vehicle were characterized by a diminished reinforcing efficacy of, and sensitivity to, sucrose. Motivational dysregulation was evidenced by enhanced drug-seeking for cocaine relative to control animals treated with vehicle. Second, treatment with SE ameliorated both motivational deficits and dysregulation in HIV-1 Tg rats. Following a history of cocaine self-administration, HIV-1 Tg animals treated with vehicle exhibited lower levels of dendritic branching and a shift towards longer dendritic spines with decreased head diameter. Treatment with SE, however, led to long-term enhancements in dendritic spine morphology in HIV-1 Tg animals supporting a potential underlying basis by which SE exerts its therapeutic effects. Taken together, SE restored motivated behavior in the HIV-1 Tg rat, expanding the potential clinical utility of SE to include both neurocognitive and affective alterations.

scholarly journals Do Prenatally Methamphetamine-Exposed Adult Male Rats Display General Predisposition to Drug Abuse in the Conditioned Place Preference Test?

2012 ◽  
pp. S129-S138
Author(s):  
R. ŠLAMBEROVÁ ◽  
M. POMETLOVÁ ◽  
B. SCHUTOVÁ ◽  
L. HRUBÁ ◽  
E. MACÚCHOVÁ ◽  
...  
Keyword(s):  
Drug Abuse ◽  
Pregnant Women ◽  
Conditioned Place Preference ◽  
Adult Male ◽  
Place Preference ◽  
Male Rats ◽  
Self Administration ◽  
Adult Rats ◽  
Drug Seeking ◽  
Seeking Behavior

Drug abuse of pregnant women is a growing problem. The effect of prenatal drug exposure may have devastating effect on development of the offsprings that may be long-term or even permanent. One of the most common drug abused by pregnant women is methamphetamine (MA), which is also the most frequently abused illicit drug in the Czech Republic. Our previous studies demonstrated that prenatal MA exposure alters behavior, cognition, pain and seizures in adult rats in sex-specific manner. Our most recent studies demonstrate that prenatal MA exposure makes adult rats more sensitive to acute injection of the same or related drugs than their controls. The aim of the present study was to examine the effect of prenatal MA exposure on drug-seeking behavior of adult male rats tested in the Conditioned place preference (CPP). Adult male rats were divided to: prenatally MA-exposed (5 mg/kg daily for the entire prenatal period), prenatally saline-exposed (1 ml/kg of physiological saline) and controls (without maternal injections). The following drugs were used in the CPP test in adulthood: MA (5 mg/kg), amphetamine (5 mg/kg), cocaine (5 and 10 mg/kg), morphine (5 mg/kg), MDMA (5 mg/kg) and THC (2 mg/kg). Our data demonstrated that prenatally MA-exposed rats displayed higher amphetamine-seeking behavior than both controls. MA as well as morphine induced drug-seeking behavior of adult male rats, however this effect did not differ based on the prenatal MA exposure. In contrast, prenatal MA exposure induced rather tolerance to cocaine than sensitization after the conditioning in the CPP. MDMA and THC did not induce significant effects. Even though the present data did not fully confirmed our hypotheses, future studies are planned to test the drug-seeking behavior also in self-administration test.

scholarly journals Methamphetamine self-administration in a runway model of drug-seeking behavior in male rats

2018 ◽  
Vol 175 ◽  
pp. 27-32
Author(s):  
Mona Akhiary ◽  
Erin M. Purvis ◽  
Adam K. Klein ◽  
Aaron Ettenberg
Keyword(s):  
Male Rats ◽  
Self Administration ◽  
Drug Seeking ◽  
Seeking Behavior

scholarly journals Pharmacological Interventions on The Dopamine Motivation System Effectively Disturbed Cue-Induced Memory Reconsolidation Cocaine-Seeking Behavior for Rats

2021 ◽  
Author(s):  
Yang Li ◽  
Nan Li ◽  
Liang Qu ◽  
Xin Wang ◽  
Ping Wang ◽  
...  
Keyword(s):  
Drug Addiction ◽  
Sch 23390 ◽  
Memory Reconsolidation ◽  
High Dose ◽  
Negative Consequences ◽  
Self Administration ◽  
Pharmacological Interventions ◽  
Drug Seeking ◽  
Motivation System ◽  
Seeking Behavior

Abstract Drug addiction is a disorder related to dysfunction in the neural reward memory circuits, and it is characterized by compulsive drug use despite terrible negative consequences. Memory reconsolidation, during which aroused memory is easy to strengthening, weakening or updating, plays an extremely important role in drug addiction. Effectively interfering with the drug memory reconsolidation process would be key in treating drug addiction, but this intervention currently remains impossible. The dopamine motivation system has been widely recognized as an important system for reward, but whether the dopamine motivation system participates in drug memory reconsolidation is unclear. We aimed to explore the role of the dopamine motivation system during the cue-induced cocaine memory reconsolidation process by examining the effect of different pharmacological interventions on the dopamine motivation system during cue-induced cocaine self-administration-related memory reconsolidation drug-seeking behavior. Using a combined behavioral and biological method, our results showed that high concentrations of SCH 23390 and raclopride, or VTA lesions, could effectively disturb subsequent cue-induced cocaine self-administration-related memory reconsolidation drug-seeking behavior in rats. However, low concentrations of SCH 23390 and raclopride could not block this behavior. In summary, only a high dose of dopamine D1 and D2 receptor antagonists, or VTA lesions, could effectively disturb subsequent cue-induced cocaine self-administration-related memory reconsolidation drug-seeking behavior. These findings indicated that pharmacological interventions in the dopamine motivation system could effectively disturb subsequent cue-induced drug memory reconsolidation. Thus, pharmacological interventions on the dopamine motivation system might have therapeutic potential for drug addiction.

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